For brevity, we discuss the specific results only for DEP; the results for NEUR and SWB are similar but more limited. For the tissues tested by DEPICT, Figure 7a plots the P values based on both the GWAS and MTAG results. As expected, nearly all of the enrichment of signal is found in the nervous system. To facilitate interpretation of the enriched gene sets, we used a standard procedure16 to group the 347 gene sets into ‘clusters’ defined by degree of gene overlap. Many of the resulting 46 clusters, shown in Figure 7b, implicate communication between neurons (‘synapse,’ ‘synapse assembly,’ ‘regulation of synaptic transmission,’ ‘regulation of postsynaptic membrane potential’). This evidence is consistent with that from the DEPICT-prioritized genes, many of which encode proteins that are involved in synaptic communication. For example, PCLO, BSN, SNAP25, and CACNA1E all encode important parts of the machinery that releases neurotransmitter from the signaling neuron.17
